During the coming year we propose to characterize possible clinically relevant mechanisms of endothelial cell injury and resultant intimal proliferative changes in the baboon. Experiments are planned using homocystine, hypercholesterolemia, hypoxia, carbon monoxide exposure, hypertension, renal failure and immune injury using specific antiendothelial cell membrane antibody. We also propose to use human endothelial cells in culture to study the effects of reduced oxygen levels, exposure to carbon monoxide, hypercholesterolemic serum and the proliferative effects of the platelet mitogenic factor. The reactivity of platelets to cultured human cells will also be examined, utilizing endothelial cells, smooth cells and fibroblasts. Proposed studies in patients include a comparative evaluation of Cr51-platelet survival and C14-serotonin platelet survival as a means to differentiate irreversible platelet consumption and reversible platelet aggregate formation respectively. Studies will be carried out on selected patients who may have platelet reactions involved in their disease process, e.g. coronary artery disease, diabetes, scleroderma, malignancy, etc. BIBLIOGRAPHIC REFERENCES: Harker, L.A.: Bleeding disorders secondary to platelet abnormalities. Current Therapy, H.F. Conn, Ed., W.B. Sanders Co., Philadelphia, 256-262, 1975. Deubelbeiss, K.A., Dancey, J.T., Harker, L.A., Chenery, B., and Finch, C.A.: Marrow erythroid and neutrophil cellularity in the dog. J. Clin. Invest. 55:825-832, 1975.